Hsl7p, a negative regulator of Ste20p protein kinase in the Saccharomyces cerevisiae filamentous growth-signaling pathway.

In the budding yeast, Saccharomyces cerevisiae, protein kinases Ste20p (p21(Cdc42p/Rac)-activated kinase), Ste11p [mitogen-activated protein kinase (MAPK) kinase kinase], Ste7p (MAPK kinase), Fus3p, and Kss1p (MAPKs) are utilized for haploid mating, invasive growth, and diploid filamentous growth. Members of the highly conserved Ste20p/p65(PAK) protein kinase family regulate MAPK signal transduction pathways from yeast to man. We describe here a potent negative regulator of Ste20p in the yeast filamentous growth-signaling pathway. We identified a mutant, hsl7, that exhibits filamentous growth on rich medium. Hsl7p belongs to a highly conserved protein family in eukaryotes. Hsl7p associates with the noncatalytic region within the amino-terminal half of Ste20p as well as Cdc42p. Deletions of HSL7 in haploid and diploid strains led to cell elongation and enhancement of both haploid invasive growth and diploid pseudohyphal growth. However, deletions of STE20 in haploid and diploid greatly diminished these hsl7-associated phenotypes. In addition, overexpression of HSL7 inhibited pseudohyphal growth. Thus, Hsl7p may inhibit the activity of Ste20p in the S. cerevisiae filamentous growth-signaling pathway. Our genetic analyses suggest the possibility that Cdc42p and Hsl7p compete for binding to Ste20p for pseudohyphal development when starved for nitrogen.

[Creative activities in home care for terminally-ill cancer patients at a rural municipal hospital].

Karuizawa Hospital is a rural, small town municipal hospital with 60 beds, located in Nagano Prefecture in central Japan. The terminal stages of patients who were treated in our department of surgery but later died of cancer are reviewed. In the five year period extending from April, 1994 through March, 1999 sixty patients died from cancer. Of them, 34 people died in their own home and 26 in our hospital. The annual ratio of patients who died at home to those who died in the hospital are analyzed, as well as whether these ratios differed according to the location of the patient's cancer. The identity of the patients' main home caregiver was sought, as well as how many days the patients resided at home until they passed away, and how frequently doctors or nurses visited their home. Some of the doctors' attempts to gain informed consent are described. Based on the findings, the authors recommend an end to the practice of first revealing the name and details of a patient's disease to his/her family. It was also found that documented information is useful in order to promote smooth relationships among patients, family members, and the doctor.

Insulin-stimulated polypeptide chain elongation in the soleus muscle of mice.

The effect of insulin on polypeptide chain elongation was examined in soleus muscles isolated from 18 hour-fasted mice. Treatment with insulin for 1 hour increased the elongation rate, which was estimated by the half-transit time. This suggests that insulin stimulated protein synthesis by modifying the elongation rate in addition to the initiation rate.

A yeast gene necessary for bud-site selection encodes a protein similar to insulin-degrading enzymes.

Cells of the yeast Saccharomyces cerevisiae choose bud sites in a non-random spatial pattern that depends on mating type: axial for haploid cells and bipolar for a/alpha diploid cells. We identified a mutant yeast, axl 1, in which the budding pattern is altered from axial to bipolar. Expression of the AXL1 gene is repressed in a/alpha diploid cells. With the ectopic expression of AXL1, a/alpha cells exhibited an axial budding pattern, thus AXL1 is a key morphological determinant that distinguishes the budding pattern of haploid cells from that of a/alpha diploid cells. AXL1 encodes a protein similar in sequence of the human and Drosophila insulin-degrading enzymes and to the Escherichia coli ptr gene product. The axial budding pattern might result from degradation of a target protein by the putative Axl1 protease.

Molecular cloning of the gene encoding a highly expressed protein in SFL1 gene-disrupted flocculating yeast.

We identified a yeast gene encoding Flocculent Specific Protein (FSP) produced excessively in the SFL1 gene-disrupted flocculent strain. The sequenced gene encodes a 430 amino acid protein and is mainly composed of multiple repeats of Ser-Asn-Asn-X-Asp-Ser-Tyr-Gly. The FSP gene disruption of the flocculent strain decreased the degree of flocculation, so FSP may be one factor concerned with yeast flocculation. A gene database search indicated that the FSP gene is identical with the DDR48 gene.